((N-heterocyclyl)carbonyl)phosphoramidothioate ester insecticides

ABSTRACT

O,S-Dailkyl ((nitrogen heterocyclyl)carbonyl)phosphoramidothioates are prepared by the reaction of O,S-dialkyl phosphoroisocyanatidothioates with selected five and six membered nitrogen heterocycles and found to be effective plant systemic and contact insecticides. Ethyl 1-(((methoxy(methylthio)phosphinyl)amino)carbonyl)-4-piperidinecarboxylate, for example, is prepared from O,S-dimethyl phosphoroisocyanatidothioate and ethyl 4-piperidinecarboxylate and found to control aster leafhopper when applied to rice plants.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of application Ser. No. 07/419,424 filed Oct. 10, 1989, now Pat. No. 5,075,293 and of application Ser. No. 7/419,056, filed on Oct. 10, 1989, now Pat. No. 5,068,230.

BACKGROUND OF THE INVENTION

The present invention relates to O,S-dialkyl ((N-heterocyclyl)carbonyl)phosphoramidothioates derived from five and six membered nitrogen heterocycles, to insecticidal compositions containing the compounds, and to the use of the compounds as insecticides.

The control of insects is critical to modern agriculture and to the maintenance of public health. Although many compounds that are useful in the control of insects are known, new compounds that are more effective, are less toxic to mammals, are more compatible with the environment, are less expensive, or have other outstanding properties, are constantly sought and when found highly valued.

Many of the compounds known to be useful in the control of insects are organophosphorus compounds. Such compounds include O,S-dimethyl phosphoramidothioate (methamidophos) and O,S-dimethyl acetylphosphoramido-thioate (acephate). Certain O,S-dialkyl N,N-dialkyl-carbamoylphosphoramidothioates and their use as insecticides is disclosed in published German Patent Applications 2,718,554 and 2,805,682. The use of these known compounds as insecticides is often limited due to their toxicological and environmental properties, their lack of persistence, and their lack of activity on certain important insects.

SUMMARY OF THE INVENTION

It has now been found that certain O,S-dialkyl ((1- heterocyclyl)carbonyl)phosphoramidothioates derived from five or six membered nitrogen heterocycles having only one nitrogen atom, which can be viewed as O,S-dialkyl N-(substituted-carbamoyl)phosphoramido-thioates in which the substituent and the nitrogen of the carbamoyl moiety form a five or six membered nitrogen heterocyclic moiety, have excellent plant systemic and contact insecticidal, acaricidal, and nematicidal activity against important species, but are relatively low in mammalian and fish toxicity.

The invention includes compounds of the formula: ##STR1## wherein R, R¹, and R² each independently represent C₁ -C₄ alkyl;

A represents --CHX--or o-phenylene;

X represents phenyl, R², CO₂ R, CONR³ ₂, CN, OR², or SR² ;

each R³ independently represents H or C₁ -C₄ alkyl:

m represents 0, 1, or 2;

n represents 1, 2, 3, or 4: and

p represents 0 or 1

with the proviso that the sum of m, n, and p is such that the nitrogen heterocyclic moiety described is a 5 or 6 membered ring.

Compositions containing insecticidal amounts of the compounds of the invention in admixture with at least one agriculturally acceptable adjuvant or carrier are useful for the control of insects. A wide variety of insects is controlled by application of insecticidal amounts of the compounds to the insects or to their locus or to plants that insects feed on or their locus. Both plant systemic and contact insecticidal activity are exhibited. Sucking insects, such as leafhoppers, are especially susceptible.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the invention include those O,S-dialkyl ((1- heterocyclyl)carbonyl)phosphoramidothioates of the formula: ##STR2## wherein R, R¹, and R² each independently represent C₁ -C₄ alkyl: A represents --CHX--or o-phenylene; X represents phenyl, R², CO₂ R, CONR³ ₂, CN, OR², or SR² ; each R³ independently represents H or C₁ -C₄ alkyl: m represents 0, 1, or 2; n represents 1, 2, 3, or 4; and p represents 0 or 1 with the proviso that the sum of m, n, and p is such that the nitrogen heterocyclic moiety described is a five or six membered ring.

The compounds of the invention can be characterized as substituted O,S-dialkyl N-(substituted-carbamoyl)phosphoramidothioate esters in which the substituted-oarbamoyl moiety is an optionally substituted five or six membered nitrogen heterocyclic moiety and optionally contains an o-phenylene moiety as a ring component or is optionally substituted at any position with a phenyl, alkyl, alkoxycarbonyl, carbamoyl, (mono- or di-)alkylcarbamoyl, cyano, alkoxy, or alkylthio group. The alkyl function in each substituent may contain one to four carbon atoms in either a straight chain or a branched chain configuration.

Compounds wherein the heterocyclic moiety is unsubstituted (a piperidine or pyrrolidine moiety) or contains a phenylene linkage (a tetrahydroquinoline or dihydroindole moiety) are sometimes preferred.

The R and R¹ substituents on the phosphorothioic acid moiety of the compounds of the invention are independently selected from either straight chain or branched chain C₁ -C₄ alkyl groups. Methyl, ethyl, propyl, isopropyl, and isobutyl are typical. Compounds wherein both R and R¹ represent methyl are often preferred as are compounds wherein R represents n-propyl and R¹ represents ethyl.

The compounds of the present invention contain an asymmetric phosphorus atom and in some cases one or more asymmetric carbon atoms and, therefore, exist as optical isomers. The present invention relates to each of these optical isomers individually and to all mixtures thereof as well as to all geometric isomers.

The compounds of the invention include, but are not limited by, the compounds illustrated in the following table.

    __________________________________________________________________________      ##STR3##                                                                                                   MP,°C. or                                                                      Elem. Anal.                                Cpd No.                                                                             R  R.sup.1                                                                           A           m n p RI@25° C.                                                                      1                                          __________________________________________________________________________      1   CH.sub.3                                                                          CH.sub.3                                                                          --          0 4 0 113-115                                                                               CHN                                         2   CH.sub.3                                                                          CH.sub.3                                                                          --          1 4 0 96     CHN                                         3   CH.sub.3                                                                          CH.sub.3                                                                          CH(C.sub.6 H.sub.5)                                                                        2 2 1 124-126                                                                               CHN                                         4   CH.sub.3                                                                          CH.sub.3                                                                           -o-phenylene                                                                              0 2 1 145-147                                                                               CHN                                         5   CH.sub.3                                                                          CH.sub.3                                                                           -o-phenylene                                                                              0 3 1 97-99  CHN                                         6   CH.sub.3                                                                          CH.sub.3                                                                           -o-phenylene                                                                              1 2 1 152-154                                                                               CHN                                         7   CH.sub.3                                                                          CH.sub.3                                                                          CH(CO.sub.2 C.sub.2 H.sub.5)                                                               0 3 1 1.5192 CHN                                         8   CH.sub.3                                                                          CH.sub.3                                                                          CH(CO.sub.2 C.sub.2 H.sub.5)                                                               0 4 1 1.5139 CHN                                         9   CH.sub.3                                                                          CH.sub.3                                                                          CH(CO.sub.2 CH.sub.3)                                                                      1 3 1 65-67  CHN                                        10   CH.sub.3                                                                          CH.sub.3                                                                          CH(CO.sub.2 C.sub.2 H.sub.5)                                                               1 3 1 1.5169 CHN                                        11   CH.sub.3                                                                          CH.sub.3                                                                          CH(CONH.sub.2)                                                                             1 3 1 132-135                                                                               CHN                                        12   CH.sub.3                                                                          CH.sub.3                                                                          CH(CH.sub.2 CO.sub.2 C.sub.2 H.sub.5)                                                      1 3 1 103-105                                                                               CHN                                        13   CH.sub.3                                                                          CH.sub.3                                                                          CH(CO.sub.2 C.sub.2 H.sub.5)                                                               2 2 1 1.5173                                            14   C.sub.3 H.sub.7                                                                   C.sub.2 H.sub.5                                                                   CH(CO.sub.2 C.sub.2 H.sub.5)                                                               0 4 1 1.5043 CHN                                        15   C.sub.3 H.sub.7                                                                   C.sub.2 H.sub.5                                                                   CH(CO.sub.2 CH.sub.3)                                                                      1 3 1 1.5117 CHN                                        16   C.sub.3 H.sub.7                                                                   C.sub.2 H.sub.5                                                                   CH(CH.sub.2 CO.sub.2 C.sub.2 H.sub.5)                                                      1 3 1 1.5064 CHN                                        17   C.sub.3 H.sub.7                                                                   C.sub.2 H.sub.5                                                                   CH(CO.sub.2 C.sub.2 H.sub. 5)                                                              2 2 1 1.5083 CHN                                        __________________________________________________________________________      .sup.1 Acceptable analyses obtained                                      

The compounds of the present invention can be prepared by the reaction of an appropriate O,S-dialkyl phosphoroisocyanatidothioate and an appropriate nitrogen heterocycle as shown in the following scheme wherein all substituents are defined as above: ##STR4##

The reaction can be conducted by combining the two starting materials in a solvent, such as ether, toluene, methylene chloride, or acetonitrile at about -10° C. to about 60° C. and allowing them to react. The product, a compound of the present invention, that forms can be recovered by conventional means, such as by evaporation of the solvent or, in the case of solids, by filtration and drying. The recovered products can be purified by conventional means, such as by liquid chromatography, by extraction with solvents in which the products are poorly soluble, or in the case of solids, by recrystallization. The compounds of the invention are generally oily liquids or colorless solids.

The starting materials for the above method are generally well known in the art or can readily be prepared using the methods taught in the art. The preparation of the isocyanatidophosphoramidothioate esters can be conveniently accomplished by heating an O,S-dialkyl phosphoramidothioate with phosgene or oxalyl chloride in a solvent. The preparation of the nitrogen heterocycle compounds varies depending on their structure; many can be prepared by reduction of the corresponding unsaturated heterocycle by known methods.

The compounds of the present invention can be used directly as insecticides, but it is generally preferable to first prepare an insecticidal composition containing one or more of the compounds in combination with an agriculturally acceptable adjuvant or carrier. Suitable adjuvants or carriers should not be phytotoxic to valuable crops, particularly at the concentrations employed in applying the compositions for insect control in the presence of crops, and should not react chemically with the insecticidal compounds or other composition ingredients. Such mixtures can be designed for application directly to plants or their locus or can be concentrates or formulations which are normally diluted with additional carriers and adjuvants before application They can be solids, such as, for example, dusts, granules, water dispersible granules, or wettable powders, or liquids, such as, for example, emulsifiable concentrates, solutions, emulsions or suspensions.

Suitable agricultural adjuvants and carriers that are useful in preparing the insecticidal mixtures of the invention are well known to those skilled in the art.

Liquid carriers that can be employed include water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, and the like. Water is generally the carrier of choice for the dilution of concentrates.

Suitable solid carriers include talc, pyrophyllite clay, silica, attapulgus clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, Fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like.

It is frequently desirable to incorporate one or more surface-active agents into the compositions of the present invention. Such surface-active agents are advantageously employed in both solid and liquid compositions, especially those designed to be diluted with carrier before application. The surface-active agents can be anionic, cationic or nonionic in character and can be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes. Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulfate: alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate: alkylphenol-alkylene oxide addition products, such as nonylphenol-C₁₈ ethoxylate: alcohol-alkylene oxide addition products, such as tridecyl alcohol-C₁₆ ethoxylate: soaps, such as sodium stearate: alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide: and salts of mono and dialkyl phosphate esters.

Other adjuvants commonly utilized in agricultural compositions include antifoam agents, compatibilizing agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, dyes, odorant, penetration aids, spreading agents, sticking agents, dispersing agents, thickening agents, freeze point depressants, antimicrobial agents, and the like. The compositions can also contain other compatible components, for example, fungicides, other insecticides, and the like and can be formulated with solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like or with liquid fertilizers.

The concentration of the active ingredients in the insecticidal compositions of this invention is generally from about 0.001 to about 98 percent by weight. Concentrations from about 0.01 to about 90 percent by weight are often employed. In compositions designed to be employed as concentrates, the active ingredient is generally present in a concentration from about 5 to about 98 weight percent, preferably about 10 to about 90 weight percent. Such compositions are typically diluted with an inert carrier, such as water, before application. The diluted compositions usually applied to insects or their locus or to plants or their locus generally contain about 0.001 to about 0.1 weight percent active ingredient and preferably contain about 0.005 to about 0.05 percent.

The present compositions can be applied by the use of conventional ground or aerial dusters and sprayers, by addition to irrigation water, and by other conventional means known to those skilled in the art.

The compounds of the invention are useful for the control of a wide variety of insects, mites, and nematodes. Sucking and chewing insects, especially sucking insects, are susceptible to the compounds. Leafhoppers, in particular, are well controlled.

The compounds are active against insect pests by both contact and plant systemic action and, consequently, can be applied either directly to the insects or to the locus thereof so that they will come in contact with the exterior parts of the insect pest or can be applied to plants insects feed on or the locus of such plants so that they will be ingested by the insect pests. It is often preferred to apply the compounds to plants or to the locus of plants and take advantage of the plant systemic properties of the compounds. The treatment of rice plants or their locus to control leafhoppers is a preferred application.

The following Examples are presented to illustrate the invention: they should not be construed as limiting.

EXAMPLES Example 1 Preparation of O,S-Dimethyl 1-Piperidinylcarbonylphosphoramidothioate

A solution of 6.0 grams (g) of O,S-dimethyl phosphoroisocyanatidothioate in 100 milliliters (ml) of ether was cooled to 0° C. and to this was added dropwise with stirring 3.1 g of piperidine. A precipitate began to form almost immediately and after one hour this precipitate was collected by filtration and extracted with ether. It was then recrystallized from toluene-hexane to obtain the title compound as white crystals melting at 96° C.

Elemental Analysis (percent): Calc. for C₈ H₁₇ N₂ O₃ PA: C, 38.08; H, 6.79: N, 11.11. Found: C, 38.12: H, 6.70: N, 11.31.

Example 2 Preparation of O,S-Dimethyl (1-(1,2,3,4-Tetrahydroquinolinyl)carbonyl)phosphoramidothioate

To a solution of 2.7 g of 1,2,3,4-tetrahydroquinoline in 60 ml of ether was added dropwise with stirring 3.4 g of O,S-dimethyl phosphoroisocyanatothioate. A precipitate began to form almost immediately and after one hour this precipitate was collected by filtration, extracted with ether, and dried under reduced pressure to obtain 5.3 g (87 percent of theory) of the title compound as white crystals melting at 97°-99° C.

Elemental Analysis (percent): Calc. for C₁₂ H₁₇ N₂ O₃ PA; C, 47.99: H, 5.71; N, 9.33. Found: C, 47.75: H, 5.67; N, 9.29.

Example 3 Preparation of Methyl 1-(((Methoxy-(methylthio)phosphinyl)amino)carbonyl)-3-piperidinecarboxylat

A solution of 8.36 g of O,S-dimethyl phosphoro-isocyanatidothioate in 100 ml of ether was cooled to 0° C. and to it was added dropwise with stirring 7.15 g of methyl 3-piperidinecarboxylate. The mixture was allowed to warm to ambient temperature and react overnight. The precipitate that formed was collected by filtration, extracted with ether, and dried under reduced pressure to obtain 11.5 g (74 percent of theory) of the title compound as white crystals melting at 65°-67° C.

Elemental Analysis (Percent) Calc. for C₁₀ H₁₉ N₂ O₅ PS; C, 38.70: H, 6.17: N, 9.03. Found: C, 38.83: H, 6.13: N, 8.94.

Example 4 Preparation of Ethyl 1-(((Ethoxy-(propylthio)phosphinyl)amino)carbonyl)-4-piperidinecarboxylate

To a solution of 2.36 g of ethyl 4-piperidine-carboxylate in 50 ml of ether at ambient temperature was added dropwise with stirring 3.14 g of O-ethyl S-n-propyl phosphoroisocyanatidothioate. The mixture was allowed to stir overnight and was then concentrated by evaporation under reduced pressure using a rotary evaporator and then a Kugelrohr apparatus at 55° C. and 13 Pascals pressure. The residue, which was the title compound, amounted to 5.2 g (94 percent of theory) and was an amber colored viscous oil having a refractive index at 25° C. of 1.5083.

Elemental Analysis (Percent) Calc. for C₁₄ H₂₇ N₂ O₅ PS: C, 45.89: H, 7.43: N, 7.65. Found: C, 45.58; H, 7.48: N, 7.45.

Example 5 Insecticidal Activity Against Aster Leafhopper

Test compounds were dissolved in a small amount of acetone and the resulting solutions were diluted with distilled water containing 0.1 percent Triton™×-100 surfactant (an octylphenol ethoxylate nonionic surfactant) to obtain application mixtures containing known amounts. Rice plants were grown in vermiculite in a greenhouse under controlled conditions.

Foliar treatments were made to determine the contact insecticidal activity. Individual rice plants were sprayed to runoff with an application mixture containing a known concentration of a test compound and then the plants were allowed to dry for one hour. Control plants were treated in the same way with a surfactant solution prepared in the same way as the application mixtures. Root treatments were made to determine the systemic insecticidal activity. Individual rice plants were transferred to an individual hydroponic system and 25 ml of an application mixture containing a known concentration of a test compound was added to the system. Control plants were treated in the same way with a surfactant solution prepared in the same way as the application mixtures.

A plastic cylinder was placed around each of the plants and 10 adult aster leafhoppers (Macrosteles severni) were placed in each cylinder. The cylinders were capped and maintained under conditions conducive to the growth of the plants and the insects. After two days the contents of each cylinder was examined to determine the percentage of the aster leafhoppers that were dead. The results were collected and an LC₅₀ (the concentration at which one half of the insects died) calculated for each compound tested. The results are given in the following table.

    ______________________________________                                         CONTROL OF ASTER LEAFHOPPERS                                                   Compound       Contact   Systemic                                              Number         LC.sub.50, ppm                                                                           LC.sub.50, ppm                                        ______________________________________                                          1             >20       >5                                                     2             >20       2.8                                                    3                10.2   0.97                                                   4                6.2    0.74                                                   5              11       0.86                                                   6              12       1.1                                                    7             >20       1.7                                                    8             >20       2.7                                                    9              13       1.7                                                   10             >20       1.4                                                   11              12       0.7                                                   12              20       2.7                                                   13               8       0.6                                                   14             >20       2.6                                                   15             >20       5.0                                                   16             >20       4.2                                                   17             >20       2.4                                                   ______________________________________                                     

What is claimed is:
 1. A compound of the formula: ##STR5## wherein R and R¹ each independently represent C₁ -C₄ alkyl;A represents --CHX--or o-phenylene; X represents phenyl, C₁ -C₃₄ alkyl, CH₂ CO₂ R, CO₂ R, or CONR³ ₂ ; each R³ independently represents H or C₁ -C₄ alkyl; m represents 0, 1, or 2; n represents 1, 2, 3, or 4; and p represents 0 or 1with the proviso that the sum of m, n, and p is such that the nitrogen heterocyclic moiety described in a five or six membered ring.
 2. A compound of claim 1 wherein p represents O.
 3. A compound of claim 1 wherein p represents one and A represents o-phenylene.
 4. A compound of claim 1 wherein p represents one and A represents CO₂ R.
 5. A compound of claim 1 wherein R and R¹ each represent methyl.
 6. A compound of claim 5, O,S-dimethyl (1-(2,3-dihydroindolyl)carbonyl)phosphoramidothioate.
 7. A compound of claim 5, methyl 1-(((methoxy(methylthio)phosphinyl)amino)carbonyl)-3-piperidinecarboxylate
 8. A compound of claim 5, ethyl 1-(((methoxy-(methylthio)phosphinyl)amino)carbonyl)-4-piperidien-carboxylate.
 9. A ninsecticidal composition comprising an agricultrually acceptable adjuvant or carrier and an insecticidally effective amount of a compound of the formula: ##STR6## wherein R and R¹ each independently represent C₁ -C₄ alkyl;A represents --CHX--or o-phenylene; X represents phenyl, C₁ -C₄ alkyl, CH₂ CO₂ R, CO₂ R, or CONR³ ₂ ; each R³ independently represents H or C₁ -C₄ alkyl; m represents 0, 1, or 2; n represents 1, 2, 3, or 4; and p represents 0 or 1with the proviso that the sum of m, n, and p is such that the nitrogen heterocyclic moiety described is a five or six membered ring.
 10. A composition of claim 9 wherein p represents O.
 11. A composition of claim 9 wherein p represents one and A represents o-phenylene.
 12. A composition of claim 9 wherein p represents one and A represents CO₂ R.
 13. A composition of claim 9 wherein R and R¹ each represent methyl.
 14. A composition of claim 13 wherein the compound is O,S-dimethyl (1-(2,3-dihydroindolyl)carbonyl)phosphoramidothioate.
 15. A composition of claim 13 wherein he compound is methyl 1(((methoxy(methylthio)phosphinyl)-amino)carbonyl)-3-piperidnecarboxylate.
 16. A composition of claim 13 wherein the compound is ethyl 1(((mthoxy(methylthio)phosphinyl)-amino)carbonyl)-4-piperidinecarboxylate.
 17. A method of controlling insects which comprises contacting the insects or the locus thereof or the plants on which the insects feed or the locus thereof with an insecticidally effective amount of a compound of the formula ##STR7## wherein R and R¹ each independently represent C₁ -C₄ alkyl;A represents --CHX--or o-phenylene; X represents phenyl, C₁ -c₄ alkyl, CzH₂ CO₂ R, CO₂ R, or CONR³ ₂ ; each R³ independently represents H or C₁ -c₄ alkyl; m represents 0, 1, or 2; n represents 1, 2, 3, or 4; and p represents 0 or 1with the proviso that the sum of m, n, and p is such that the nitrogen heterocyclic moiety described is a five or six members ring.
 18. A method of claim 17 wherein p represents O.
 19. A method of claim 17 wherein p represents one and A represents o-phenylene.
 20. A method of claim 17 wherein p represents one and A represents CO₂ R.
 21. A method of claim 17 wherein R and R¹ each represent methyl.
 22. A method of claim 21 wherein the compound is O,S-dimethyl (1-(2,3-dihydroindolyl)carbonyl)phosphoramidothioate.
 23. A method of claim 21 wherein the compound is ethyl 1-(((methoxy(methylthio)phosphinyl)amino)-carbonyl)-4-piperidinecarboxylate.
 24. A method of claim 21 wherein the compound is ethyl 1-(((methoxy(methylthio)phosphinyl)amino)-carbonyl)-4-piperidinecarboxylate.
 25. A method of claim 17 wherein the insects controlled are sucking insects.
 26. A method of claim 25 wherein the insects are leafhoppers.
 27. A method of claim 17 wherein the plants are rice plants. 